Despite current drug therapies, including those that target enzymes, channels and known G-protein-coupled receptors (GPCRs), cardiovascular disease remains the major cause of ill health, which suggests that other transmitter systems might be involved in this disease. In humans, approximately 175 genes have been predicted to encode 'orphan' GPCRs, where the endogenous ligand is not yet known. As a result of intensive screening using 'reverse pharmacology', an increasing number of orphan receptors are being paired with their cognate ligands, many of which are peptides. The existence of some of these peptides such as urotensin-II and relaxin had been known for some time but others, including ghrelin and apelin, represent novel sequences. The pharmacological characterization of these emerging peptide-receptor systems is a tantalising area of cardiovascular research, with the prospect of identifying new therapeutic targets.

中文翻译：

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孤儿G蛋白偶联受体在心血管系统中的新兴作用。

尽管当前的药物疗法包括针对酶，通道和已知的G蛋白偶联受体（GPCR）的药物疗法，但心血管疾病仍然是健康状况不佳的主要原因，这表明该疾病可能涉及其他递质系统。在人类中，据预测大约有175个基因编码“孤儿” GPCR，而内源性配体尚不清楚。使用“反向药理学”进行严格筛选的结果是，越来越多的孤儿受体与其同源配体配对，其中许多是肽。其中一些肽的存在，例如尿紧张素-II和松弛素，已经存在了一段时间，但其他肽，包括生长素释放肽和阿佩林，则代表了新的序列。